Objective: To investigate the different-dose effects of methamphetamine (METH) on spatial learning and memory and the possible mechanisms. Methods: C57BL/6 mice were treated with 0.5, 1.0 and 2.0 mg/kg of METH or normal saline. The drug was injected intraperitoneally 30 min prior to the Morris water maze. All mice experienced 5 consecutive days' positioning navigation experiment and the spatial exploration experiment conducted 24 hours after the last training trial. Immediately after the probe test, the mice were killed by cervical dislocation and the hippocampus was dissected. Western blot was used to detect changes in phosphorylation levels of extracellular signal-regulated kinase (ERK1/2) and cAMP response element-binding protein (CREB) in the hippocampus. Results: Compared with the mice in saline group, those in 1.0 mg/kg METH group had a significantly shorter latency (P<0.05), spent more time in the target quadrant (P<0.05), and had more platform site crossings (P<0.05). Moreover, 0.5 and 2.0 mg/kg of METH did not significantly affect the mice's spatial learning and memory, but 0.5 mg/kg of METH showed a memory-promoting trend, while 2.0 mg/kg of METH showed a memory-destroying trend. METH of 1.0 mg/kg significantly increased p-ERK1/2 (P<0.05) and p-CREB (P<0.05) levels in the hippocampus. Conclusion: METH of 1.0 mg/kg significantly improved mice's spatial learning and memory. The effect of METH is an inverted U-curve among three doses of METH at 0.5, 1.0 and 2.0 mg/kg. ERK1/2 and CREB in the hippocampus may be involved in METH-induced improvement of spatial learning and memory in mice.

Objective: This study was designed to evaluate the therapeutic efficacy of bronchial arterial infusion with VDS＋ DDP or MMIC＋ ADM＋ DDP in patients with locally advanced nonsmall cell lung cancer(NSCLC). Methods: From June 1992 to October 1998,102 patients with locally advanced NSCLC were enrolled in this study. Of them,8 cases in Stage Ⅱ , 72 cases in Stage Ⅲ a, 22 cases in Stage Ⅲ b, central type: 75 cases,peripheral type:27 cases;preliminary group 64 cases, secondary group 38cases. The patients were treated one to four times by bronchial arterial infusion of the chemical drugs Results: There were 3 complete responses and 66 partial responses for an overall responses rate of 67.65％ (69/102) including responses rate of 72.00％ (54/75) in central type and 55.56％ (15/27), the 1-year and 2-years survival rate was 67.64％ (69/102)and 36.28％ (37/102) respectively. Conclusions: The therapeutic efficacy of bronchial arterial infusion with chemical drugs was excellent to locally advanced non small cell lung cancer, it′ s toxicity were acceptable. The efficacy on central was much better than for peripheral type

AIMTo study the effect of recombinant hirudin (rH) on tPA-induced fibrinolysis and the possible mechanism of its action.

METHODSThe effect of rH on thrombin-fibrin complex (Th-Fn) was detected by 99mTc labeled rH. In the in vitro clot lysis, tPA as plasminogen activator, and recalcified plasma as plasminogen resource were used to study the influence of rH on fibrinolysis by detecting TAFIa, D-Dimer and FXIII.

RESULTSIn a canine model of femoral artery thrombosis, a clear radioactivity strip was imaged in 30 - 60 min on a part image, and the femoral vein thrombosis developed at 30 min. rH efficiently inhibited clot regeneration. Addition of TM could inhibit clot lysis obviously, and CPI could shorten the delay of clot lysis which due to TAFIa. There was a dose-dependent relationship with TM concentration and TAFI activation. FXIII activation was inhibited by low concentration of rH ( < or = 0.2 u x mL(-1)), and the level of fibrinolysis product, D-Dimer, increased.

CONCLUSIONrH could inhibit the thrombin binding to fibrin. rH inhibited the activation of TAFI and FXIII by combining with thrombin which resulted in enhancement of thrombolysis.

Animals ; Blood Coagulation ; drug effects ; Carboxypeptidase B2 ; metabolism ; Carboxypeptidases ; antagonists & inhibitors ; Dogs ; Factor XIII ; metabolism ; Femoral Artery ; Femoral Vein ; Fibrinolysis ; drug effects ; Fibrinolytic Agents ; pharmacology ; Hirudins ; genetics ; pharmacology ; Male ; Plant Proteins ; pharmacology ; Protease Inhibitors ; Recombinant Proteins ; pharmacology ; Thrombomodulin ; metabolism ; Thrombosis ; metabolism ; Venous Thrombosis ; metabolism

Objective To explore the changes in neuroglobin(NGB)expression in rat cerebral cortex induced by acute and chronic hypoxia at high altitude.Methods Seventy SD rats were randomly divided into normal control and experimental groups,and in the latter group,the rats kept in a high-altitude research base in Kekexili(4600 m),while the control rats were kept in a facility at the altitude of 2295 m.The rats in the experimental group were divided into 6 groups with the exposure time of 12,24,48,72 h,1 week and 1 month.An oximeter was used to measure the SaO2 level.Semi-quantitative PCR and Western blotting were performed to detect the expression levels of NGB mRNA and protein in the cortical neurons of the rats after the exposure.Results After explosure of the rats to hypoxia at high altitude for 12h,the SaO2 was lowered to(70.70±2.83)%and increased gradually as exposure time prolonged,but remained lower than that in the control group throughout the exposure.RT-PCR showed a rapid increase of NGB mRNA expression after 24-h exposure to hypoxia,followed by gradual decrease till recovery of the normal level at 1 week;the expression slowly increased after 1 week and maintained a high level till 1 months.showing significant difference from that in the control group(P＜0.05).Western blotting showed an identical pattem of NGG protein expression alterations during the experiment.Conclusion NGB expressions in the cerebral cortex increase significantly after acute and chronic hypoxia at an altitude of 4600 m to enhance the tolerance to hypobaric hypoxia,suggesting the possible role of NGB as an important endogenous mechanism for protecting the neural tissues against hypoxic injuries.

Methods of reverse transcription polymerase chain reaction (RT-PCR), intrathecal injection and antisense drugs were used to study the effects of nitric oxide (NO) on the scores of morphine-withdrawal syndrome and the expression of NMDA1AR mRNA in rat spinal cord and brainstem. Intrathecal injection of NOS antisense oligonucleotides (AS-ONs) significantly decreased the scores of morphine-withdrawal symptoms. The effect of nNOS AS-ONs was greater than that of eNOS AS-ONs. The expression of NMDA1AR mRNA in the spinal cord and brainstem increased in morphine-dependent rats and increased to a greater extent in morphine-withdrawal rats. Intrathecal injection of nNOS AS-ONs significantly inhibited the increased expression of NMDA1AR mRNA in the spinal cord and brainstem of morphine-withdrawal rats. Intrathecal injection of eNOS antisense oligonucleotides inhibited the expression of NMDA1AR mRNA in the spinal cord of morphine-withdrawal rats, but did not in the brainstem. It is suggested that NO mediates morphine-withdrawal reaction and participates in modulating the expression of NMDA1AR mRNA in morphine-withdrawal rats.

OBJECTIVESepsis and septic shock remain a common problem that results in significant mortality and morbidity in pediatric intensive care units (PICU). According to literature, the use of more physiologic steroid replacement therapy is associated with hemodynamic and survival benefits in adult patients with relative adrenal insufficiency (RAI) and catecholamine-resistant septic shock. But little information is available in children. The aim of the current prospective study was to determine the prevalence of adrenal insufficiency in children with sepsis and septic shock using a low-dose adrenocorticotropic hormone (ACTH) stimulation test (1 microg/1.73 m2) in children.

METHODSThe authors performed cortisol estimation at baseline and after low-dose (1 microg/1.73 m2) ACTH stimulation at 30 mins in children during the first 24 hours in patients with sepsis or septic shock admitted to our PICU. Adrenal insufficiency was defined as a response < or = 90 microg/L. Absolute adrenal insufficiency (AAI) was further defined as baseline cortisol (T0) < 200 microg/L and RAI insufficiency by T0 > or = 200 microg/L.

RESULTSSixty-two consecutive cases with sepsis and septic shock admitted to PICU of Shanghai Jiaotong University Affiliated Children's Hospital from April, 2006 to March, 2007. The median age was 37.6 months (range, 2 - 168 months), and their gender distribution was 42 (67.7%) males and 20 (32.3%) females, 53 cases had sepsis (85.5%) and 9 had septic shock (14.5%). The mean pediatric critical illness score (PCIS) was 79.3 +/- 9.2 and median pediatric risk of mortality score (PRMSIII) 11.3 (5 - 19), respectively. Overall mortality of sepsis and septic shock was 27.42%. The evaluation of adrenal insufficiency was conducted as follows. (1) The mean cortisol levels at baseline (T0) and 30 mins after ACTH stimulation (T1) were (318.6 +/- 230.4) microg/L, (452.3 +/- 230.7) microg/L and (454.7 +/- 212.7) microg/L, (579.3 +/- 231.9) microg/L in patients with severe sepsis and septic shock group, respectively. There were no significant difference between the two groups (P > 0.05). (2) The proportion of patients with adrenal insufficiency in the study population was 40.3% as defined by a response < or = 90 microg/L post test. The proportion of patients with adrenal insufficiency in sepsis and septic shock were 39.6% and 44.4%, respectively (chi2) = 0.073, P > 0.05). (3) The serum T0 and T1 levels were (320.5 +/- 223.9) microg/L, (462.3 +/- 212.0) microg/L and (384.3 +/- 258.3) microg/L, (500.7 +/- 470.6) microg/L, respectively, and the proportion of patients with adrenal insufficiency were 37.8% and 47.1% in the survivors and the dead (P > 0.05). The levels of T0 and T1 were related to the PCIS (P < 0.05). The morbidity of adrenal insufficiency was not related to the PCIS, PRISMIII, and number of organ that developed functional insufficiency (P > 0.05).

CONCLUSIONSAdrenal insufficiency may occur in patients with sepsis and septic shock in children. ACTH stimulation test may be helpful to determine whether corticosteroid therapy has a survival benefit in patients with relative adrenal insufficiency. A low-dose ACTH stimulation test can be used to evaluate the adrenal function status of severe sepsis and septic shock in children.

Adolescent ; Adrenal Insufficiency ; diagnosis ; etiology ; Adrenocorticotropic Hormone ; metabolism ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Intensive Care Units, Pediatric ; Male ; Prospective Studies ; Sepsis ; physiopathology ; Shock, Septic ; physiopathology ; Systemic Inflammatory Response Syndrome ; physiopathology

OBJECTIVETo explore the effects of survivin antisense RNA on taxol-induced apoptosis in leukemia cell line HL-60.

METHODSA survivin antisense eukaryotic vector pcDNA3-SVVas was transferred into HL-60 cells by electroporation. The live fraction was determined by trypan blue dye exclusion assay. Cell counting and MTT assay were performed to evaluate the sensibility of the transfected cells to taxol. Apoptosis was detected by DNA gel electrophoresis and nuclear staining.

RESULTSTwo positive cell clones, HL-60 SVVas and HL-60 neo were obtained. Compared to HL-60 and HL-60 neo cells, HL-60 SVVas cells growth was significantly reduced (P < 0.05). By MTT assay, the IC(50) of taxol to HL-60 SVVas, HL-60 neo and HL-60 cells were (14.4 +/- 1.87) ng/ml, (31.9 +/- 6.38) ng/ml and (32.0 +/- 3.52) ng/ml, respectively, the difference was significant by statistic analysis (P < 0.01). Agarose gel electrophoresis of genomic DNA from HL-60 SVVas showed typical DNA ladder, but DNA from HL-60 neo and HL-60 did not. Nuclei become condense in HL-60 SVVas cells.

CONCLUSIONSurvivin antisense RNA could enhance taxol-induced apoptosis in leukemia cell line HL-60. This may lay an experimental foundation for further research of gene therapy in leukemia.

Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Drug Synergism ; HL-60 Cells ; Humans ; Inhibitor of Apoptosis Proteins ; Microtubule-Associated Proteins ; genetics ; Neoplasm Proteins ; genetics ; Paclitaxel ; pharmacology ; RNA, Antisense ; genetics ; pharmacology ; Transfection

AIMTo explore the effects of tRNA on the growth of mammalian cells.

METHODSL929, NIH3T3, MCF-7 and PC12 cells were seeded in 96 well culture plate individually, and incubated at 37 degrees C in 5% CO2 for 4 h, the tRNAs from different species were added to the culture media individually. After certain time of incubation, the viability of the cells was evaluated by the MTT methods. Sub-confluent L929 cells were incubated with 200 microg/ml ytRNA for different times, then the cells were pooled and analyzed with flow cytometry assay.

RESULTStRNA specifically inhibited the growth of L929 cells in a dose-dependent manner. The sizes of tRNA-treated cells showed larger sizes and longer processes than those of untreated cells. Flow cytometric analysis further showed that most of tRNA-treated cells were arrested in S phase of the cell cycle.

CONCLUSIONThe cell growth inhibitory effects of tRNAs were caused mainly by their degraded fragments. The results suggested that tRNA or its degraded fragments might play important roles in regulation of cell proliferation.

Animals ; Cell Cycle Checkpoints ; physiology ; Cell Line ; Cell Proliferation ; Fibroblasts ; cytology ; Flow Cytometry ; Mice ; RNA, Transfer ; physiology

OBJECTIVETo investigate the anti-HIV constituents from the root of Mirabilis jalapa.

METHODThe compounds were isolated by column chromatography on silica gel, Sephadex LH - 20, MCI-gel CHP-20P and RP-18. The structure were identified by means of NMR and MS analyses (1H-NMR, 13C-NMR, MS).

RESULTEleven compounds were isolated and identified as astragaloside II (1), astragaloside II (2), astragaloside IV (3), astragaloside VI (4), flazin (5), 4'-hydroxy-2, 3-dihydroflavone 7-beta-D-glucopyranoside (6), gingerglycolipid A (7), 3, 4-dihydroxybenzaldehyd (8), p-hydroxybenzaldehyde (9), beta-sitosterol (10) and daucosterol (11).

CONCLUSIONCompounds 1-9 were obtained from this genus for the first time.

Benzaldehydes ; analysis ; chemistry ; Carbolines ; analysis ; chemistry ; Chromatography, Gel ; Furans ; analysis ; chemistry ; Galactolipids ; analysis ; chemistry ; Magnetic Resonance Spectroscopy ; Mass Spectrometry ; Mirabilis ; chemistry ; Plant Roots ; chemistry ; Sitosterols ; analysis ; chemistry

OBJECTIVETo investigate the effect of allergic rhinitis (AR) and its intervention on disease condition and medications in patients with juvenile-onset systemic lupus erythematosus (JSLE).

METHODSThe clinical data of 96 children diagnosed with JSLE were collected, and according to the presence or absence of AR or other allergic diseases, they were divided into AR group (n=44), non-AR group (n=20), and non-allergic group (n=32). The children in the AR group were randomly administered with or without intervention (n=22 each). All the children were given standard JSLE treatment. The systemic lupus erythematosus disease active index (SLEDAI) and application of hormones and immunosuppressants were compared between groups.

RESULTSThe AR and non-AR groups had significantly higher SLEDAI scores, daily cumulative doses of glucocorticoids, and number of types of immunosuppressants used than the non-allergic group before treatment (P<0.05), while there were no significant differences between the AR and non-AR groups (P>0.05). After one month of treatment, the AR group with intervention had significantly lower SLEDAI scores and daily cumulative doses of glucocorticoids than the AR group without intervention (P<0.05), while there was no significant difference in the application of immunosuppressants between these two groups (P>0.05). After 3 and 6 months of treatment, the AR group with intervention had significantly lower SLEDAI scores, daily cumulative doses of glucocorticoids, and number of types of immunosuppressants than the AR group without intervention (P<0.05).

CONCLUSIONSJSLE combined with allergic diseases such as AR has an adverse effect on disease condition and treatment, and the intervention for AR helps with the control of JSLE.

Adolescent ; Child ; Child, Preschool ; Female ; Glucocorticoids ; therapeutic use ; Humans ; Immunosuppressive Agents ; therapeutic use ; Interleukin-17 ; blood ; Interleukins ; Lupus Erythematosus, Systemic ; drug therapy ; immunology ; Male ; Rhinitis, Allergic ; complications ; Severity of Illness Index